Arkuda Therapeutics, a start-up based in Cambridge, Massachusetts, has raised $44 million in series A financing to develop a small-molecule therapy for a rare neurodegenerative disease called GRN-related frontotemporal dementia (FTD-GRN).
FTD-GRN affects about 5,000–6,000 people in the US and causes severe personality changes, Arkuda CEO Gerhard Koenig says. It arises from a single mutation in the GRN gene, which makes a protein called progranulin. Those proteins are secreted by cells like macrophages and microglia. Progranulin itself is cleaved into a variety of smaller granulin peptides. Some of those are important for properly functioning lysosomes, which clean up trash in the cell.
The start-up has developed a small-molecule drug candidate to boost levels of progranulin in cells. Though Koenig won’t disclose the molecule’s drug target at this time, he says it is not a histone deacetylase inhibitor—an epigenetic drug that is known to boost progranulin levels but that changes the expression of many genes.
Academic groups have shown that reducing levels of a protein called sortilin—with genetic manipulation or a small molecule—increases progranulin levels by suppressing the endocytic degradation of progranulin.
Arkuda was founded in February 2018 by Koenig, the medicinal chemist Duane Burnett, and Bruce Booth of Atlas Venture. Atlas Venture and Pfizer Ventures led the financing. Arkuda plans to begin a clinical trial of its compound in 2021, and Koenig says the firm is investigating the potential of progranulin-boosting therapy to treat additional neurodegenerative diseases.